The goal of this proposed research is to prepare synthetic or semi- synthetic mitomycin analogs which have improved therapeutic ratios in cancer chemotherapy. The plan is based upon a knowledge of chemical and physical properties of the mitomycins, such as their hydrophilicity and quinone reduction potentials, and the application of this knowledge to exploit differences between cancer and normal cells. It involves preparing mitomycin A by fermentation and using it for semi-synthetic routes to mitomycin analogs. Total synthetic routes to analogs also will be developed. The serum inactivation of certain mitosene analogs which have potent antibacterial activity in culture will be investigated since it has bearing on potential antitumor applications. This investigation will aid the design of subsequent analogs. Antitumor assays will be conducted by the DRD Branch.